The long-term objectives of the proposed research are: on a fundamental level, an understanding of the arachidonate-related physiological regulatory mechanisms of cardiovascular elements - platelets, endothelium, and vascular tone; on a practical level, to provie or disprove the structure of thromboxane A2 (TXA2), to define the substrate specificity of the enzymes involved in conversion of arachiodonic acid to TXA2, to develop TXA2 mimics, TXA2 agonists, and specific enzyme inhibitors. We propoe to chemically synthesize 10, 10-difluoro-TXA2 (FTA2) and compare this material with biologically synthesized FTA2 produced enzymatically from chemically synthesized 10, 20-difluoro arachidonic acid and 10, 10-difluoro PGH2 methyl ester. These compounds and side-chain analogs will be evaluated for biological activity by platelet aggregometry and infusion in non-sedated, chaired baboons fitted with arteriovenous cannulae. The A-V shunted baboon is an experimental model for arterial thromboembolism. This data will aid in the development of therapeutic agents for the treatment of cardiovascular conditions not satisfactorily controlled with current drugs.